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HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals.

Publication ,  Journal Article
Burkardt, DD; Zachariou, A; Loveday, C; Allen, CL; Amor, DJ; Ardissone, A; Banka, S; Bourgois, A; Coubes, C; Cytrynbaum, C; Faivre, L; Lees, M ...
Published in: Am J Med Genet A
October 2019

Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome. Since the initial description of five unrelated individuals with three different heterozygous protein-truncating variants (PTVs) in the HIST1H1E gene in 2017, we have recruited 30 patients, all with HIST1H1E PTVs that result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain. The identification of 30 patients with HIST1H1E variants has allowed the clarification of the HIST1H1E syndrome phenotype. Major findings include an ID and a recognizable facial appearance. ID was reported in all patients and is most frequently of moderate severity. The facial gestalt consists of a high frontal hairline and full lower cheeks in early childhood and, in later childhood and adulthood, affected individuals have a strikingly high frontal hairline, frontal bossing, and deep-set eyes. Other associated clinical features include hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Brain magnetic resonance imaging (MRI) is frequently abnormal with a slender corpus callosum a frequent finding.

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Published In

Am J Med Genet A

DOI

EISSN

1552-4833

Publication Date

October 2019

Volume

179

Issue

10

Start / End Page

2049 / 2055

Location

United States

Related Subject Headings

  • Syndrome
  • Phenotype
  • Mutation
  • Learning
  • Intellectual Disability
  • Humans
  • Histones
  • Heterozygote
  • Growth and Development
  • Facies
 

Citation

APA
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ICMJE
MLA
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Burkardt, D. D., Zachariou, A., Loveday, C., Allen, C. L., Amor, D. J., Ardissone, A., … Tatton-Brown, K. (2019). HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals. Am J Med Genet A, 179(10), 2049–2055. https://doi.org/10.1002/ajmg.a.61321
Burkardt, Deepika D’Cunha, Anna Zachariou, Chey Loveday, Clare L. Allen, David J. Amor, Anna Ardissone, Siddharth Banka, et al. “HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals.Am J Med Genet A 179, no. 10 (October 2019): 2049–55. https://doi.org/10.1002/ajmg.a.61321.
Burkardt DD, Zachariou A, Loveday C, Allen CL, Amor DJ, Ardissone A, Banka S, Bourgois A, Coubes C, Cytrynbaum C, Faivre L, Marion G, Horton R, Kotzot D, Lay-Son G, Lees M, Low K, Luk H-M, Mark P, McConkie-Rosell A, McDonald M, Pappas J, Phillipe C, Shears D, Skotko B, Stewart F, Stewart H, Temple IK, Mau-Them FT, Verdugo RA, Weksberg R, Zarate YA, Graham JM, Tatton-Brown K. HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals. Am J Med Genet A. 2019 Oct;179(10):2049–2055.
Journal cover image

Published In

Am J Med Genet A

DOI

EISSN

1552-4833

Publication Date

October 2019

Volume

179

Issue

10

Start / End Page

2049 / 2055

Location

United States

Related Subject Headings

  • Syndrome
  • Phenotype
  • Mutation
  • Learning
  • Intellectual Disability
  • Humans
  • Histones
  • Heterozygote
  • Growth and Development
  • Facies